Recent work has indicated that neural stem cells are present in adult mice and can be grown in long-term liquid culture. This has formed the impetus for a collaborative group of investigators with quite varying backgrounds to work together to fully characterize the normal murine embryo, post-natal and adult brain derived neural stem cells in both in vitro and in vivo systems as a base for developing approaches to evaluate mechanisms underlying the development of glioma and preclinical models for the biologic therapy of glioma. The Program project consists of 4 scientific projects, 2 laboratory cores and an administrative core. Project 1 focuses on neurotrophic stimulation of neuro progenitors while project 3 deals with transplantation of these neural stem cells to characterize in vivo behavior and address their ability to restore function. Project 4 focuses on the ability of Trka receptor transduction to alter the biologic behavior of C6 glioma cells. A support core for the separation of neurosphere derived cells by fluorescent activated cell sorting while another Core will be maintaining neurosphere cells in culture and glioma cell line cells for the use of all projects. In total these studies are designed to develop unique models which in turn should form a base for new clinical approaches to the therapy of glioma.